Netrin‐1 alleviates subarachnoid haemorrhage‐induced brain injury via the PPARγ/NF‐KB signalling pathway

Abstract

Netrin‐1 ( NTN ‐1) is a novel drug to alleviate early brain injury following subarachnoid haemorrhage ( SAH ). However the molecular mechanism of NTN ‐1‐mediated protection against early brain injury following SAH remains largely elusive. This study aims to evaluate the effects and mechanisms of NTN ‐1 in protecting SAH ‐induced early brain injury. The endovascular perforation SAH model was constructed using male C57 BL /6J mice, and recombinant NTN ‐1 was administrated intravenously. Mortality rates, SAH grade, brain water content, neurological score and neuronal apoptosis were evaluated. The expression of PPAR γ, Bcl‐2, Bax and nuclear factor‐kappa B ( NF ‐κB) were detected by Western blot. Small interfering RNA specific to NTN ‐1 receptor, UNC 5B, and a selective PPAR γ antagonist, bisphenol A diglycidyl ether ( BADGE ), were applied in combination with NTN ‐1. The results suggested that NTN ‐1 improved the neurological deficits, reduced the brain water content and alleviated neuronal apoptosis. In addition, NTN ‐1 enhanced PPAR γ and Bcl‐2 expression and decreased the levels of Bax and NF ‐κB. However, the neuroprotection of NTN ‐1 was abolished by UNC 5B and BADGE . In conclusion, our results demonstrated that NTN ‐1 attenuates early brain injury following SAH via the UNC 5B PPAR γ/ NF ‐κB signalling pathway.

Perampanel, an AMPAR antagonist, alleviates experimental intracerebral hemorrhage‑induced brain injury via necroptosis and neuroinflammation

“…The severity of brain injury was determined by evaluating the neurological function of mice at 72 h after ICH, using our previously described neurological grading system ( 33 ). The scoring system consisted of six tests, and the specific standards are listed in the Table SI .…”

“…The severity of brain edema was evaluated by measuring the brain water content using the standard wet-dry method, as previously reported ( 15 , 33 , 34 ). The mice were sacrificed 72 h following ICH, and the entire brain was harvested and separated into the ipsilateral and contralateral cortex, ipsilateral and contralateral basal ganglia, and cerebellum (wet weight).…”

Tauroursodeoxycholic acid attenuates neuronal apoptosis via the TGR5/ SIRT3 pathway after subarachnoid hemorrhage in rats

“…TUNEL assay was conducted as previously described with modifications [ 20 ]. TUNEL reaction mixture (50 μL) was added on each sample, and the slides were incubated in a humidified dark chamber for 60 min at 37 °C.…”

Exposure to the environmental pollutant bisphenol A diglycidyl ether (BADGE) causes cell over-proliferation in Drosophila

“…This not only demonstrates that genes involved in regulating cell proliferation are transcriptionally more active, but also that cell proliferation in at least one system (hematopoietic) is significantly increased upon chronic exposure to BADGE. The peroxisome proliferator-activated receptor-gamma (PPARγ) has been linked to BADGE responses (Chen et al 2019;Dworzanski et al 2010;Nakamuta et al 2002). However, there is no obvious PPARγ homolog in Drosophila, which suggests the involvement of additional molecular pathways that need to be identified in the future.…”